Main checkpoints of the JNK-MAPK pathway using the Boolean network
simulation following HTLV-1-associated leukemia
Abstract
The c-Jun N-terminal kinase (JNK) pathway is a signal transduction
pathway that plays a critical role in cell growth and survival. Its
dysregulation is related to various cancers, including Adult T-cell
Leukemia/Lymphoma (ATLL), an aggressive peripheral T-cell malignancy due
to infection with the Human T-cell lymphotropic virus type 1 (HTLV-1).
ATLL currently has no vaccine or definitive treatment. This research
aimed to identify the JNK-MAPK pathway checkpoints to suggest possible
therapeutic targets using Boolean network analysis. First, the involved
genes and their interactions in the JNK pathway were identified and
mapped. Next, a boolean network analysis was performed using the R
programming language, which suggested Protein kinase B (AKT) and MAP
kinase phosphatase (MKP) for further evaluation. Finally, to confirm the
effect of these two genes, a case-control study was conducted among ATLL
patients and healthy individuals. The quantitative reverse transcription
polymerase chain reaction (qRT-PCR) method showed a statistically
significant decrease in the expression of AKT and MKP in ATLL patients
compared to the normal group. This highlights the potential role of
these two genes as therapeutic targets in ATLL.